Programme(s) to which this project applies: |
☑ MPhil/PhD | ☑ MRes[Med] | ☒ URIS |
Ophthalmic disorders such as retinal dystrophies and age-related macular degeneration represent rapidly growing disease areas, but few effective treatments are currently available. Advances in molecular biology in past decades have led to the discovery of many proteins with promising therapeutic potentials, including cytokines and neurotrophic factors. Yet, one obstacle is the lack of appropriate drug delivery system. Existing approaches such as topical application (e.g. eye drops) and conventional administration (e.g. oral, intravenous) limit the entrance of most molecules into retina. Direct intraocular injection can be problematic because of relatively short half-life of the agents in vivo and therefore obligatory repeated injections, which is a burden to patients with chronic retinal degenerative retinal disorders.
There arises a need for better intraocular delivery of the therapeutic molecules such that a consistent supply of the agents is available for prolonged period of time. Encapsulated cell therapy (ECT) with encapsulation of engineered cells can achieve long-term and continuous drug delivery. We previously have successfully optimized the use of collagen and alginate, two natural biomaterials in a composite gel, collagen-alginate composite (CAC) based on the ECT concept. Our CAC ECT device exhibits good tensile strength and good biostability. Long-term release of bioactive glial-derived neurotrophic factor (GDNF) from prolonged CAC ECT device implantation improved retinal cellular structure and electrophysiological function in the rat model of retinal degeneration. However, well-trained personnel and long preparation period are required for fabricating the CAC ECT device, thereby limiting its future application in clinical settings. Moreover, the volume of the current CAC ECT device was limited to 2 ul for rat eyes. As the human eye is much larger, patients may require multiple intravitreal injections of the current CAC ECT device in order to achieve effective drug concentrations in the vitreous, which could cause potential injuries to the retina and the eye. It is essential to upscale the CAC ECT device to achieve efficacy with fewer intravitreal injections. Another important aspect would be automation of CAC ECT device production.
In this proposal, we aim to develop the CAC ECT device via microfluidics technology and achieve an automated high-throughput yield in a time-saving production but with better reproducibility.
Professor ACY Lo, Department of Ophthalmology
Professor Amy Lo obtained her PhD from the Department of Neuroscience in the Johns Hopkins University School of Medicine. One of the PI's research themes is neuroprotection in the eye using disease models such as transgenic and knockout mice, rats and rabbits as well as in vitro models using primary cells and cell lines. She is well trained in morphological, functional, cellular, and molecular analyses of the eye and brain. Professor Amy Lo has been using genetic and pharmacological manipulations to identify potential therapeutic targets for various ocular diseases. She has track record on age-related macular degeneration, diabetic retinopathy, cerebral and retinal ischemia/reperfusion injury, oxygen-induced retinopathy, retinal degeneration, and intraocular drug delivery.
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